Tissue level, activation and cellular localisation of TGF-β1 and association with survival in gastric cancer patients

Autor: W. van Duijn, F.J.G.M. Kubben, Kim Zuidwijk, Lukas J. A. C. Hawinkels, Hein W. Verspaget, Jan H. Verheijen, Cornelis B.H.W. Lamers, J. M. Van Der Zon, Daan W. Hommes, Cornelis F. M. Sier
Přispěvatelé: TNO Kwaliteit van Leven
Rok vydání: 2007
Předmět:
Male
Cancer Research
Pathology
Biomedical Research
correlation analysis
medicine.medical_treatment
transforming growth factor beta1
urokinase
Matrix metalloproteinase
fibroblast
smooth muscle
cancer survival
Stomach cancer
comparative study
stomach mucosa
stomach cancer
adult
article
Transforming growth factor-β
transforming growth factor-β
protein function
Middle Aged
Immunohistochemistry
enzyme activity
female
Cytokine
priority journal
Oncology
Female
ELISA
proteinase
tumour microenvironment
medicine.drug
medicine.medical_specialty
matrix metalloproteinase
Stromal cell
protein localization
Biology
Transforming Growth Factor beta1
Stomach Neoplasms
medicine
Humans
human
Molecular Diagnostics
protein expression
Aged
Urokinase
Tumour microenvironment
tissue homogenate
Cancer
medicine.disease
major clinical study
microenvironment
Survival Analysis
human tissue
myofibroblast
enzyme linked immunosorbent assay
smooth muscle actin
epithelium cell
Transforming growth factor
Zdroj: British Journal of Cancer, 3, 97, 398-404
British Journal of Cancer
ISSN: 1532-1827
0007-0920
Popis: Transforming growth factor-beta1 (TGF-beta1), a tumour suppressing as well as tumour-promoting cytokine, is stored as an extracellular matrix-bound latent complex. We examined TGF-beta1 activation and localisation of TGF-beta1 activity in gastric cancer. Gastric tumours showed increased stromal and epithelial total TGF-beta1 staining by immunohistochemistry. Active TGF-beta1 was present in malignant epithelial cells, but most strongly in smooth muscle actin expressing fibroblasts. Normal gastric mucosa from the same patient showed some staining for total, and little for active TGF-beta1. Active TGF-beta1 levels were determined by ELISA on tissue homogenates, confirming a strong increase in active TGF-beta1 in tumours compared to corresponding normal mucosa. Moreover, high tumour TGF-beta1 activity levels were significantly associated with clinical parameters, including worse survival of the patients. Total and active TGF-beta1 levels were not correlated, suggesting a specific activation process. Of the different proteases tested, active TGF-beta1 levels were only correlated with urokinase activity levels. The correlation with urokinase activity suggests a role for plasmin in TGF-beta1 activation in the tumour microenvironment, resulting in transformation of resident fibroblasts to tumour promoting myofibroblasts. In conclusion we have shown localisation and clinical relevance of TGF-beta1 activity levels in gastric cancer.
Databáze: OpenAIRE
Externí odkaz: